Journal article
3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening
LJ Hale, SE Howden, B Phipson, A Lonsdale, PX Er, I Ghobrial, S Hosawi, S Wilson, KT Lawlor, S Khan, A Oshlack, C Quinlan, R Lennon, MH Little
Nature Communications | Published : 2018
Abstract
The podocytes within the glomeruli of the kidney maintain the filtration barrier by forming interdigitating foot processes with intervening slit diaphragms, disruption in which results in proteinuria. Studies into human podocytopathies to date have employed primary or immortalised podocyte cell lines cultured in 2D. Here we compare 3D human glomeruli sieved from induced pluripotent stem cell-derived kidney organoids with conditionally immortalised human podocyte cell lines, revealing improved podocyte-specific gene expression, maintenance in vitro of polarised protein localisation and an improved glomerular basement membrane matrisome compared to 2D cultures. Organoid-derived glomeruli retai..
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Awarded by Royal Children's Hospital Foundation
Funding Acknowledgements
We thank Moin Saleem, University of Bristol for the provision of the conditionally immortalised podocyte cell line. RNA sequencing was performed by the Translational Genomics Unit, Murdoch Children's Research Institute. We thank the family of the patient described in this study and we acknowledge the KidGen consortium, particularly Andrew Mallett, for recruitment ethics. iPSC patient line derivation was performed by iPSC Core Facility, Murdoch Children's Research Institute. Mass spectrometry was performed in the Biomolecular Analysis Core Facility, University of Manchester, UK and supported by fellowship funding (to R.L.) from the Wellcome Trust (202860/Z/16/Z). M. C.R.I. is supported by the Victorian Government's Operational Infrastructure Support Program. We also thank the Centre for Advanced Histology and Microscopy at the Peter MacCallum Cancer Centre for assistance with scanning electron microscopy. A.O. is an NHMRC Career Development Fellow. M.H.L. is an NHMRC Senior Principal Research Fellow (GNT1136085). This work was supported by the National Health and Medical Research Council of Australia (GNT1098654), the National Institutes of Health (DK107344-01) and the Royal Children's Hospital Foundation for funding of the ReGeniPS program.